Which immunologic process is primarily affected by the proteasome inhibitor bortezomib in patients with relapsed multiple myeloma?

Bortezomib, a proteasome inhibitor, primarily affects the presentation of antigens to CD8+ T lymphocytes. The proteasome plays a crucial role in the degradation of intracellular proteins, including those that are tagged for destruction due to being damaged or misfolded. This process is essential for generating peptide fragments that are then transported to the endoplasmic reticulum, where they are loaded onto major histocompatibility complex (MHC) class I molecules.

Once these peptide-MHC class I complexes are formed, they are transported to the cell surface, allowing CD8+ T lymphocytes to recognize and respond to these displayed antigens. In the context of multiple myeloma, where tumor cells can evade immune detection, bortezomib's inhibition of the proteasome disrupts this pathway, leading to altered antigen presentation. This can enhance the ability of the immune system to recognize and attack malignant cells.

The other processes listed, such as the activation of the complement cascade, activation of perforin, and secretion of histamine by mast cells, do not have a direct connection with the effects of a proteasome inhibitor like bortezomib. Complement activation, for instance, involves a series of proteins